- M7824 is an investigational immunotherapy that is designed to bring together both
anti-transforming growth factor-beta and anti-PD-L1 mechanisms
- Data to be presented at ASCO 2018 show M7824's anti-tumor activity in patients with
advanced non-small cell lung cancer and advanced human papillomavirus associated
cancers
- M7824 continues to be explored in tumors and settings where addressing both mechanisms
could lead to improved clinical outcomes

Merck KGaA, Darmstadt, Germany, a leading science and technology company which operates its healthcare business in the U.S. and Canada as EMD Serono, today announced results from expansion cohorts of the ongoing M7824 Phase I clinical trial (NCT02517398) program at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting in Chicago, June 1-5, 2018. These data include results in patients with advanced non-small cell lung cancer (NSCLC) and in human papillomavirus (HPV) associated cancers (NCT03427411), presented in collaboration with the National Cancer Institute (NCI), providing further evidence that bringing together a transforming growth factor-beta (TGF-beta) trap with the anti-PD-L1 mechanism may generate clinically relevant anti-tumor activity.

"M7824's dual approach to fighting cancer, which brings together a TGF-beta trap with the anti-PD-L1 mechanism, complements our existing immuno-oncology portfolio," said Luciano Rossetti, M.D., Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany. "The unique design of this fusion protein offers the potential to optimally engage the TGF-beta pathway. This is one example of the creative approaches we are taking to address challenging cancers where we believe we can deliver a transformational change for patients."

In patients with second line (no prior immunotherapy) advanced NSCLC from the cohort of the ongoing Phase I clinical trial (NCT02517398), signs of clinical activity were seen across PD-L1 expression levels. At the recommended Phase II dose (1200 mg every 2 weeks), an investigator-assessed confirmed overall response rate (ORR) of 40.7% (11/27 patients) was observed in patients with PD-L1+ tumors (greater than or equal to1%, Ab clone 73-10). In patients with high PD-L1+ expressing tumors (greater than or equal to80%; Ab clone 73-10 [greater than or equal to80% as measured with Ab clone 73-10 comparable with tumor proportion score (TPS) greater than or equal to50% with 22C3]), ORR was 71.4% (5/7 patients). A median progression-free survival (PFS) of 6.8 months was observed for PD-L1+ patients (1200 mg every 2 weeks) and the median PFS was not reached for the high PD-L1-expressing population owing to the number of patients still responding at the time of analysis. Safety data in this study were consistent with those observed in the overall M7824 Phase I clinical program. The most common treatment-related adverse events (TRAEs) were pruritus (20.0%), maculopapular rash (18.8%) and decreased appetite (12.5%). Grade 3 TRAEs were experienced by 21 patients (26.3%), Grade 4 TRAEs occurred in 2 patients (2.5%). The most common events were skin and subcutaneous tissue disorders. Eight patients (10%) discontinued treatment due to TRAEs.

From the ongoing Phase I, open-label trial NCT03427411 (presented in collaboration with the NCI), signs of tumor burden reduction were seen in 47% (8/17 patients) of patients with advanced HPV associated cancers, including cervical, anal, or head and neck squamous cell carcinoma, enrolled in the dose escalation part of the study. The ORR was 35.3% in patients with HPV associated cancer and 41.7% (including 1 patient with response post-pseudoprogression) in patients with proven HPV-positive disease (12 patients). Safety data in this study were consistent with those observed in the broader M7824 clinical program. A total of 4 patients (23.5%) experienced Grade greater than or equal to3 TRAEs, including colitis, cystitis, gastroparesis, pleural effusion and hypokalemia (Grade 4); notably, 3 of these patients had tumor burden reduction. No other Grade 4 or 5 TRAEs were seen.

M7824 is an investigational bifunctional immunotherapy that brings together a TGF-beta trap and 'fuses' it with the anti-PD-L1 mechanism. M7824 is designed to simultaneously block the two immunosuppressive pathways and control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is an important part of a novel combination approach that seeks to harness the power of the immune system and address the tremendously complex nature of difficult-to-treat tumors such as NSCLC and HPV associated cancers. These data build on a number of recent readouts for M7824, including preliminary data in gastric cancer at the ASCO 2018 Gastrointestinal Cancers Symposium. Merck KGaA, Darmstadt, Germany, will present data from additional cohorts in hard-to-treat cancer types in the coming year.

In addition to M7824, data from a number of high-priority clinical development programs are also being presented at ASCO 2018, including tepotinib (NSCLC), M2698 (advanced tumors) and two molecules from the DNA Damage Response portfolio (advanced solid tumors).

Merck KGaA, Darmstadt, Germany, is committed to exploring an array of targets and taking creative scientific approaches to developing novel therapies for hard-to-treat cancers. With the belief that rational combination is key to the development of potential new and more efficacious treatment options, the company has a particular focus on combination treatment approaches, whether it be with chemotherapy/radiotherapy, other targeted therapies and/or immunotherapies from its own or partners' portfolios.

M7824 is an investigational bifunctional immunotherapy that is designed to bring together a TGF-beta trap and 'fuse' it with the anti-PD-L1 mechanism. M7824 is designed to simultaneously block the two immunosuppressive pathways - targeting both pathways aims to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is currently in Phase I studies for solid tumors.

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About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Almost 53,000 employees work to further develop technologies that improve and enhance life - from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2017, Merck KGaA, Darmstadt, Germany, generated sales of EUR 15.3 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany, holds the global rights to the "Merck" name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.